The present invention is related to chemical processes. More particularly, it is concerned with an improved chemical process for the preparation of 2-.beta.-D-ribofuranosylselenazole-4-carboxamide.
European patent application No. 0 072 977 to Starks Associates, Inc. discloses a method of preparing 2-.beta.-D-ribofuranosylthiazole-4-carboxamide and its utility as an antiviral/antitumor agent.
Srivastava et al., J. Med. Chem., 26:445-448 (1983), have reported the synthesis of the biologically active selenium analog, 2-.beta.-D-ribofuranosyl-selenazole-b 4-carboxamide, involving a step in which a precursor, 2,3,5-tri-O-benzoyl-.beta.-D-ribofuranosyl-1-carbonitrile is reacted in a pressure vessel with liquified hydrogen selenide in excess, serving both as reagent and solvent. This process involves a number of serious disadvantages, especially when the process is employed to produce large quantities of the desired 2-.beta.-D-ribofuranosylselenazole-4-carboxamide as, for example, on a commercial scale.
First, in either laboratory scale synthesis or when scaled up for commercial production, the use of large quantities of the highly toxic hydrogen selenide presents serious safety hazards. Hydrogen selenide is approximately 200 times as toxic as hydrogen cyanide, and extreme care must be exercised in handling the material.
Second, since the prior art process employs an excess of the liquid form of hydrogen selenide, there are required the additional steps of liquifaction of the hydrogen selenide prior to reaction, and the removal of the excess reagent following reaction. This method adds both complexity and additional safety hazards to the overall process.
Third, the prior art process requires extended reaction periods for the step in which hydrogen selenide is reacted with the starting compound. This often results in anomerization of the desired product to the unwanted alpha-anomer. Separation of the alpha- and beta-amomeric forms of the product introduces additional costly and time-consuming steps.